This comprehensive and unique research program concerns the investigation on the interrelationship between aging and carcinogenesis, in both human and Syrian hamster cells, and their correlations between in vitro and in vivo results. This program is based on full cooperation between the Johns Hopkins group (with expertise in carcinogenesis and Syrian hamster model) and Dr. E.L. Schneider's laboratory (with expertise in senescence and human studies), Gerontology Research Center, NIA. This program consists of the following five projects: 1. Characterization of fibroblast populations to be used for in vitro senescence and neoplastic transformation research. Two subprojects: (a) The identification, quantitation, and characterization of contact-insensitive cells (putative stem cells) and senescent cells. (b) The establishment of Syrian hamster fibroblasts as a model system for in vitro and in vivo aging studies. 2. In vitro neoplastic transformation of human cells and its relationship to senescence and somatic mutation. 3. Interrelationship (s) between growth/senescence and neoplastic transformation/somatic mutation in the Syrian hamster model. 4. Application of cell biology and somatic genetics to the study of senescence of cells in culture. Three subprojects: (a) Manipulation of the senescence process. (b) The relationship (s) between senescence and somatic mutation. (c) The relationship (s) between senescence and ploidy. 5. Development of new technology for the study of in vitro senescence and neoplastic transformation. Five subprojects: (a) New assays for neoplastic transformation. (b) New assays for tumor formation by transformed human and hamster cells in nude mice. (c) Liposomes as carriers of enzymes and other important biological substance. (d) Immunological tools for the detection of cell surface properties of transformed cells, putative stem cells, and non-senescent cells. (e) Molecular biology techniques (2D-gel analysis, nucleic acid hybridization) for the analysis of the change in function/structure of the genetic apparatus upon senescence and transformation. The innovative concept of this research is to study senescence by focusing the attention on "escape from senescence" a required step for neoplastic transformation.